Thanks for signing up! You might also like these other newsletters:

Medications for Crohn’s disease and ulcerative colitis are constantly changing, and it’s often difficult to keep up with the latest treatment developments. In this Crohn's and Colitis Foundation of America program, Dr. Edward Loftus, Jr., of the Mayo Clinic in Rochester, Minnesota, discusses current and future treatments for Crohn's disease and ulcerative colitis and how they may work for you. He talks about exciting advances in the development of biologic medications – which target the chemical mediators of inflammation that trigger Crohn’s and colitis flares – and other medications that may be available in the future.

Similarities and Differences Among Crohn's, Colitis and IBD

Dr. Loftus:

Crohn's disease causes inflammation in various parts of the gastrointestinal tract. It can affect anywhere from the mouth all the way down to the anal area. Oftentimes the inflammation is a full thickness inflammation, and this can result in a variety of symptoms depending on the location and severity of the inflammation. This could include diarrhea, abdominal pain, fatigue, but even symptoms in other organ systems, such as joint aches or pains.

Ulcerative colitis, on the other hand, is a bowel condition that affects the colon only, and it only affects the innermost layer of the bowel, the mucosa. Various parts of the colon can be affected, but it's going to localize itself to the colon. This can result in symptoms such as rectal bleeding, diarrhea, and urgency, such as a pressing need to use the restroom, and it can also cause fatigue, sometimes abdominal cramping and some of these extra-intestinal manifestations that I alluded to with Crohn's disease.

And if you combine these two conditions, it turns out that maybe as many as 1.1 to 1.5 million people in the United States have these conditions.

IBD are the inflammatory bowel diseases, Crohn's and UC, whereas IBS, irritable bowel syndrome, is something completely different. IBS is really something to do with the way our nervous systems in the gut are wired, almost as if there is a hypersensitivity in the gut. So some of the symptoms are similar. You can get diarrhea and abdominal pain, but you can also get constipation. The symptoms tend not to be accompanied by findings such as anemia or pain that wakes you up at night or blood in the stool. Certainly blood in the stool you would never attribute to IBS.

What Are the Most Common Treatments for Crohn's Disease?

Dr. Loftus:

You could categorize five general classes of treatments. The first class would be the aminosalicylates, sometimes called 5-aminosalicylates or 5-ASA medications. And this would include an old standby that's been around for 60 years, sulfasalazine, also known as Azulfidine, and then agents that are derivatives of that.

The newer 5-ASA agents are mesalamine, which is basically 5 ASA by itself. There are several products. There is one called Asacol, which is a pH-dependent release molecule that releases in the ileum [end of the small intestine] and in the colon. There is Pentasa, which is a time-dependent release in the small intestine and in the colon. And then you have mesalamine given topically in medicated suppositories. The brand name for that is Canasa. Mesalamine enemas come in generic form, and there is an older form that many of us are familiar with called Rowasa.

There are several other 5-ASA derivatives. One is called balsalazide, or Colazal, and this is a capsule released in the colon. And then there is olsalazine, or Dipentum, which is also orally administered but then delivers into the colon. So there are a wide variety of 5-ASA agents, and they all contain the same active ingredient.

Antibiotics are another general classification. We think that antibiotics work because they decrease the levels of bacteria within the gut, not killing a specific bug, but reducing bacterial levels so there is less stimulus for the gut immune system to react to. The two antibiotics we use most frequently are metronidazole (Flagyl) and ciprofloxacin (Cipro), but there are other antibiotics we use as well.

Steroids are a nonspecific modulator of inflammation. The most commonly used one is prednisone given orally, but we use other types. Hydrocortisone can be administered as a suppository or as a medicated enema. There is a specially derived steroid called budesonide (Entocort) which is sometimes used in Crohn's disease. Because of the way it's designed, most of it is metabolized in the liver before it has a chance to cause side effects in the rest of the body.

Immunomodulators would include medications like azathioprine (Imuran or Azasan), 6-mercaptopurine (Purinethol), and methotrexate. The idea here is that the immune system is dysregulated, and if we can tamp down the immune system a bit, it will result in decreased inflammation. We most commonly use these medications in people who are having trouble weaning off of steroids or every time they wean off steroids, they have a flare-up of their condition.

Biologics are antibodies or antibody derivatives, so these are what we call monoclonal antibodies. These are basically biotechnology engineered molecules that are directed specifically against a particular substance in the inflammatory pathway. The first example of this in IBD was a medication called infliximab, or Remicade, and this was directed against a specific molecule called tumor necrosis factor (TNF) alpha. Now there are two additional medications, adalimumab (Humira) and certolizumab pegol (Cimzia), which are now approved for use in Crohn's disease. Infliximab, on the other hand, is approved for both Crohn's disease and ulcerative colitis.

There is a fourth biologic agent that became available earlier this year for Crohn’s called natalizumab (Tysabri), which is directed against a specific adhesion molecule. Adhesion molecules are molecules that are expressed on white blood cells or along the lining of blood vessels that enable the white blood cell to home in on areas of inflammation, then get out of the blood vessel and migrate to where it needs to go.

The inflammatory cascade is incredibly complex so these various drugs are targeting various parts of that inflammatory cascade, and some are more effective than others. Ideally, we would like to find the root cause for what's triggering this whole response, and to date we haven't found it.

Risks and Benefits of Standard Crohn's Disease Medications

Dr. Loftus:

When I am talking to people with ulcerative colitis and Crohn's disease, there's this constant balancing of the benefits of medications with potential risks. In general, as the effectiveness of a medication increases, the chance of having a side effect increases too.

The 5-ASA agents are pretty safe and well-tolerated. The occasional person has an allergic reaction to them. They might get a rash. Rarely will we see kidney complications, and it's usually recommended that, if you are on a 5-ASA medication, to have kidney function monitoring perhaps once a year. Rarely, you might see something unusual like pancreatitis with those agents.

The antibiotics are generally well-tolerated. The occasional person might be allergic to them. Sometimes they can cause worsening diarrhea, so we always have to be careful and individualize the antibiotic treatment.

Steroids are beneficial in the short term. They are our fire extinguisher for flares, but people can gain weight, they get insomnia, their face [swells] up. They can get acne. They get very moody or angry or anxious. And then there are the long-term side effects. Steroids can leach calcium from the bones, cause osteoporosis and high blood pressure, and make blood sugar control more difficult if you have diabetes. If a person can't wean off of steroids without having a flare-up, then usually the next step is to use the immunomodulators like azathioprine or 6-MP. But these medications aren't free of side effects. You have to monitor blood counts for low white blood cell count, and about three percent of people can get pancreatitis with these agents. All told, if you took a group of a hundred people and put them on azathioprine, maybe 15 of them wouldn't be able to stay on it because they would experience these side effects. There is some controversy about whether azathioprine and 6-MP and, to a lesser extent, methotrexate are associated with lymphoma. It's a controversial area, but there are some studies suggesting a very weak link with lymphoma, and I always hate to bring that up because the benefit of the drug far outweighs that theoretical risk, which is less than one in 1,000, but that risk is potentially out there.

Finally, with the biologics there is a risk of reactivating certain dormant infections. And there is a risk of other unusual infections, such as fungal infections, and that same potential risk with lymphoma that still remains controversial. It's hard to tease all of that out because: A, is the disease itself associated with lymphoma; B, is it related to another medication; or, C, is it related to the drug itself?

Natalizumab (Tysabri) is the one biologic agent that was actually initially approved by the FDA (Food and Drug Administration) for multiple sclerosis, and after it was on the market for a few months, it got pulled off because there were three people in clinical trials (out of roughly 3,000) who developed a very unusual but severe neurologic side effect called PML, or progressive multifocal leukoencephalopathy. So the drug was pulled off the market temporarily, and then they reintroduced it in a restricted program where as long as you are not on another immune suppressing medication you can get this medication. For some patients who have not responded to the anti-TNF medications such as Remicade or Humira this might be a good option.

Not All Alternative Treatments for Crohn's and Colitis Are Safe or Effective

Dr. Loftus:

There have been some interesting studies that show that up to 50 percent, perhaps even more, of patients with IBD seek complementary and/or alternative therapies.

Now, which alternative or complementary therapies should we recommend? Many patients with IBD are at risk for vitamin and mineral deficiencies, so at a minimum, at some point somebody should be checking them for fat-soluble vitamin deficiencies. Fat-soluble vitamins are A, D, E and K. Crohn's patients are at risk for vitamin B12 deficiencies. Both UC and Crohn's patients are at risk for iron deficiency. Many of these deficiencies can be easily treated.

Another popular alternative therapy is fish oil, and I see that many people are on that, but we should all realize that in the Journal of the American Medical Association (JAMA) they recently published two large, very well designed trials of fish oil in Crohn's disease and could not demonstrate any benefit. In other words, it did not prevent people from having flares of their Crohn's disease. So there are often these initial flurries of enthusiasm for alternative medications, but when you study them rigorously, it doesn't always hold up.

I think there are things that are more holistic things like relaxation techniques or breathing techniques, for some people, prayer – these are fine. I get concerned when people are using herbal supplements. That whole industry has a lot less regulation, and we have heard in the last couple of years about things that are contaminated from China or other places. I think there is a quality-control issue with some of these supplements that I would be very, very concerned about. In most cases these complementary, alternative substances have not been rigorously studied, so it's hard for me to recommend them.

Now having said that, some of them are interesting and make sense – the probiotics, for example. There are actually animal models where genetically engineered mice where given a certain probiotic, and they don't get gut inflammation. So that sounds like a really promising area of research. The problem is that the treatment trials that have been done to date have not shown convincing evidence that they actually work.

If you are not ingesting unknown substances into your body, it’s probably okay, and if you want to try them, that's fine, but when you start getting into herbal supplements, I would just be very cautious.

Ulcerative Colitis Treatments Emphasize 5-ASAs

Dr. Loftus:

Essentially, most of the treatments are the same [for ulcerative colitis and Crohn’s]. In ulcerative colitis there is much more of an emphasis on the use of the 5-ASA agents. All of the 5-ASA agents have FDA approvals for ulcerative colitis and not for Crohn's disease, and there is a reason for that. So I think there is a heavier emphasis on 5-ASA medications and perhaps less of an emphasis on antibiotics. And the only biologic that's currently approved for ulcerative colitis is infliximab, or Remicade. There is a sense that if it comes to surgery, surgery for ulcerative colitis is going to be a more definitive answer for somebody than surgery for Crohn's disease, because with Crohn's disease there is the risk of recurrence after surgery.

But having said that, there are issues with having surgery for ulcerative colitis, too. Some people develop problems with their J pouch. If they have one of these pouch surgeries, they could get pouchitis (inflammation of the ileal pouch).

Those are the main differences [in treatment for ulcerative colitis]: more 5 ASAs, infliximab for the biologics, and then more consideration for surgery.

Future Treatments for Crohn's and Colitis Will Be More Targeted

Dr. Loftus:

If you look at the pipeline now compared to ten years ago, there have been a huge number of developments. There are many different types of molecules being studied for Crohn's disease. There are more anti-TNF molecules. There are more of these adhesion molecules, and some may be more specific for the gut. There are molecules directed against an inflammatory substance called interleukin 12/23, another one against interleukin 17. There is one against what we call a co-stimulatory pathway, and this drug, abatacept (Orencia), is already approved for rheumatoid arthritis. There was an interesting study where you actually had blood filtered, and they took out activated white blood cells. The trial for ulcerative colitis looks like it was a negative trial, but I don't believe the results from the Crohn's disease trial have been published yet.

So these are some of the types of treatments that are out there in the pipeline, and I think there is a lot of room for hope. If you look at examples of other diseases where there have been breakthrough discoveries, oftentimes the discovery for what causes the condition comes out of left field, and you wouldn't have necessarily predicted it based on the research. This whole area of biologics is very promising, and if we can target these important inflammatory molecules, that's going to be an important area. Obviously TNF has been an important molecule, but there are other biologics in the pipeline.

I think we always worry we are missing something really obvious. You look back over 50 years, and these diseases were much less common. It's interesting watching over different parts of the world where they never saw IBD, and now they are starting to see it. As a country becomes more industrialized and more like a Western country, they start seeing more IBD. So is it something else entirely? Is there an environmental trigger that we are missing? Is it in the food? Is it in the water supply? Is it a toxin? I don't know, but I always worry about that in the back of my mind.

There are many challenges ahead with the treatment of Crohn's and colitis, and certainly no one medication has universal benefit. But with the right approach, with a doctor who is familiar with the condition, a particular medication or combination of medications may be helpful in controlling symptoms. And the good news is that in the last year we have seen lots of new treatments, and then we look in the research pipeline, and there are even more treatments in the pipeline.

Information About Treatments for Crohn's Disease and Ulcerative Colitis